CONVERSION OF BIOMANUFACTURING PROCESSES FROM FED-BATCH INTO INTEGRATED CONTINUOUS: STRATEGY, METHODS AND CASE STUDIES

摘要

Integrated continuous manufacturing offers great productivity advantages over the traditional fed-batch and therefore reduces production scale, facility footprint, and manufacturing costs. Recent advancement in process and control technologies, equipment capabilities, and automation has paved the way for the biopharmaceutical industry to start adapting processes to continuous manufacturing for clinical and commercial products. As we shift to these approaches, strategies and methodologies need to be established for introducing and developing continuous processes. Ideally, a platform continuous process would be established. Aspects to consider for the platform include cell line, cell culture media, process equipment, and a framework of process parameters that are all tailored to fit continuous manufacturing. Once established, the platform will allow shortened process development timelines, easy adaptation from one molecule to another, and improved efficiency of tech transfer into GMP manufacturing. For processes that are in late clinical development or in commercial manufacturing, with an existing fed-batch cell culture process, a process conversion strategy should be established. In these cases, existing development and characterization of the original fed-batch process can be leveraged for unit operations that are constant or similar from fed-batch to continuous. The platform continuous process can be adapted, and toolboxes can be created during the product-specific process development. The ultimate goal is to deliver robust continuous cell culture manufacturing processes with faster timeline and less development cost. This presentation will illustrate the strategy taken in Novartis with a few case studies.